Nitric Oxide in Ovarian Cancer Treatment - Essay Example

The Role of Nitric Oxide 1 The Role of Nitric Oxide in the Development and Treatment of Cancer. The Role of Nitric Oxide 2 Introduction: Cancer and Tumor. Cancer is a disease which arises due to the cell growth developing in abnormal multiples. There are many types of cancer; the subject of discussion is Ovarian Cancer. “Cancer occurs when cells undergo a transformation and begin to grow and multiply without normal controls, as the cells grow and multiply, they form masses called tumors”[eMedicine.com 2006]. Researches say that these tumor cells excels the preexisting healthy cells in the human body in terms of absorbing the oxygen and nutrients that are essential for survival and functioning of the human body. Ovarian Cancer is a type of cancer that arises in the ovaries of the female. The ovaries are the reproductive organs that produce ova which later help in the production of fetal when it contacts with the sperm of the male. Ovaries are a pair of small organs that produces human eggs or ova and also produces hormones as estrogen. Ovarian cancer occurs when a tumor forms in one or both of the women’s ovaries” [eMedicine.com 2006]. As a result the women who develop this cancer might have digestion problem, “such as indigestion, constipation, or a feeling of fullness The Role of Nitric Oxide 3 light meal, bloating, distention or cramping, abdominal or low-back discomfort , frequent urination , vomiting, pain or swelling in the abdomen. Loss of appetite, unexplained weight loss etc.”[Gale, Thomas. 2006]. These are some of the symptoms of ovarian cancer. But it seems to come for those women who are above 65. Researches say that this type of cancer could be stopped from further development of the tumor cells. While analyzing the causes it seems there is not a specific reason behind the ovarian cancer, but researches say that it might have a combined reason form the family history. “Women who .have never been pregnant or had children. .are Caucasian, especially of Northern European or Ashkenazi Jewish descent .are over 50 . have a family history of breast, ovarian, endometrial [uterine]. Prostrate or colon”[ Gale, Thomas. 2006] The pathogenesis of ovarian cancer involves staging such as involving one or both ovaries with tumor found on the surface of the ovary, then slowly extends to the fallopian tubes, then extends to outside of the pelvis, The Role of Nitric Oxide 4 and finally the metastases takes place where the woman becomes completely surrendered to tumor cells. The endocrine changes occur in hormonal imbalances and irregular menopauses. The risk factors includes “spread of cancer to other organs, progressive functions loss of various organs, ascites [fluid in the abdomen], blockage of the intestines”[Wikiepedia.edu.2006]. The recent therapies that are used to treat this ovarian cancer are almost the same as that of other cancer types. Chemotherapy and Radiation therapy are applied to treat the ovarian cancers. But recent researches show that Nitric oxide can be used in treating the ovarian cancer. Nitric oxide has been so far considered as a toxic chemical, but recent readings and researches have proof over the fact that nitric oxide . Nitric oxide has generated an exponential amount of research since its identification in 1987. During the past decade this small molecule has emerged as an important medicator in physiological and pathological processes [ De Belder, Radomski, 1994] Arguments have been running throughout the world regarding the application of nitric oxide in the treatment of cancers, that whether nitric oxide works in reducing the spread of cancerous cells or increases the The Role of Nitric Oxide 5 development of the same cells. NO [Nitric Oxide] is the product of the conversion of L-arginive to L-cytrulline by nitric oxide synthetase[NOS]. The wide variety of roles described for NO can be placed into one of the three categories. [i] An intracellular signal, [ii]. A transcellular messenger, [iii]. A cytotoxic species.[Knowles, Moncada 1994]. Nitric oxide is considered by most of the physicians and research people both as a biological medicate and as a messenger involving in physiological and pathological process of the cancer. But at the same time it might result in the damage of cells and DNA, if it is produced in an unregulated manner. Most of the cellular components as the tumor mass [tumor cells themselves, and the immune cells infiltrate] have been shown to generate NO in vitro. The depression of NOS [Nitric Oxide Synthesis] in neoplasm provokes the question about a physiological role for tumor associated NO production .[ Murtaet.al.1999] The role of tumor suppressor gene product p53 also has a significant role in the tumor development and suppression depending upon the level and consistency of the gene and NO. P53 has been found out by many scientists that it stops the formation of the tumor cells but it could enhance the growth The Role of Nitric Oxide 6 of the tumor cells if it works in combination with NO. The website on Genome called Genome.ad [2006] has released a journal over p53 and its functions it says that “In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein[p21] that interacts with a cell division –stimulating protein [cdk2].” P53 has dual role to play in cancer cells. It can suppress the growth of tumor cells in connection with NO. Over emulsion of p53 content can lead to transformation of cells. Where as the normal function of the p53 genes will result in the formation anti-oncogenes. Genome.ad [2006] also points out that “The screening of DNA from colon cancer patients revealed that p53 mutations occur with unusually high frequency in tumor tissue, an observation that was extended to most of the other major types of human cancer” However Pnas.org [2006] reports that “exposure of human cells to NO generated from an NO donor or form over expression of inducible nitric oxide synthase [NOS2] results in p53 accumulation” The main thing is that high level of NO and metabolism of NO in larger amount can cause DNA damage and have been shown to be mutagenic. The No has the tendency to induce p53 accumulation, this is the normal function The Role of Nitric Oxide 7 , where as P53 acts as mediator in the transrepression of inducible NOS. On the whole the link between p53 and NO shows that the maintenance of significant level of p53 and NO can suppress the tumor cells’ growth. Where as increased NO production might result in p53 mutation which in turn will be working in such a way that it contributes to human tumor progression. Sp p53 is called as the tumor suppressor only in connection with the NOS. While this argument goes on one side Weimngxu, Liu Lizhi, Loizidoo Marilena , Mohamed Ahmed and Charles.G [2002] has to contribute the fact that “The family of nitric oxide synthesis [NOS] comprises inducible NOS [iNOS], endothelial NOS[eNOS] and neuronal NOS [ nNOS]. Interstinlg, various studies have shown that all three isotope can be involved in promoting or inhibiting the etiology of cancer, NOS activities has been deducted in tumor cells and associated with tumor grade proliferation rate and expression of important signaling components associated with cancer development such as the estrogen receptor” They further argue that “NO and reactive level activity can have the genotoxic and angiogenic progression”[Weimngxu, 2002]. The Role of Nitric Oxide 8 The ovarian cancer is one of the endocrine system tumors. The Endocrine system produces glands and makes these glands to secrete hormones directly in to the blood stream. Ovarian cancer is also an organ secreting hormones directly into the blood stream, so the chances of tumor cells spreading become more. “A woman has two small ovaries in the pelvic area . They contain the egg cells and secrete the hormones progesterone and estrogen” [Endocrine System Tumors. 2002]. Research factors leading to the role Nitric oxide [NO] have two controversial argument. One side the argument is continued in favor of using or applying Nitric oxide as a medicator and on another side it has been still under the dispute by some research people who say that NO application of treating diseases such as tumor or cancer cannot be accepted, as NO Is still considered as a toxic factor. Modulation of NO level in tumors is a strategy for altering tumor hemodynamics and thus improving oxygen, drug, gene vector, and effector cell delivery to solid tumors.[ The American Journal of Pathology 1997]. While considering the role of Nitric oxide in the immune system it “helps the immune system’s macrophages, the cells in the body that are activated in The Role of Nitric Oxide 9 injury and illness to get rid of debris. When they seek out invading bacteria or cancer cells to destroy” [Wright, Pearce 1996] . Before that the biological and clinical applications of Nitric oxide has to be viewed , Wright, Pearce 1996] says that NO controls limitless range of functions in the body, controls the circulation of the blood, regulates the activities of the brain, lungs, liver, kidneys, stomach, gut, gentis and other organs and NO is used bythe immune system in fighting all viral, bacterial and parasitic infections and tumors”[ Wright, Pearce 1996]. However, it is possible that the role of NO in tumor cell initiation, promotion, progression, survival and apoptosis depends on the cell types, the concentrations of NO in the given cellular microenvironment, time of cellular exposure to NO , and possibly other factors” [ Cellegy.com 2006].The role of NO in tumor progression seems to be a bit controversial, since researches have not given an authorized result on how much NO applications have been successful in treating tumors and cancers. The NO inactivates tumor suppressor oncogene p53 [Cellegy.com 2006]. There are many literatures that talk in favor of the NO in cancer treatment, but the fact The Role of Nitric Oxide 10 is that some existing researchers and physicians do not agree with the view that NO could be used as positive factor for treating many diseases. While Nitric oxide transmits messages between nerve cells and is associated with the process of learning, memory, sleeping, feeling, pain and probably depression [ Wright, Pearce. 1996], Complications caused by problems with endothelial production of nitric oxide from a variety of causes: the fragile layer of endothelial calls are prone to damage, from among other things, high blood pressure, high sugar in diabetes, furring up with cholesterol and other lipids, and the effect of smoking” [Wright, Pearce. 1996]. Perhaps some more researches show that Nitric oxide plays an important role in the development of tissues and cells. But the only thing that is realized by many scientists is that nitric oxide could be considered as a biological factor helping in the development of the cells. [ Sherwood. W. Peter [2001] supports this argument by saying that “The idea that a gas could act endogenous biological messenger in mammals was an entirely new biological concept. This discovery earned Robert Furchgott, Louis Ignarro, and Ferid Murad the Noble Prize in 1998. Nitric oxide holds the record as The Role of Nitric Oxide 11 the smallest, lightest molecule –and the first gas—known to act as a biological messenger in mammals. The journal Science dubbed nitric oxide its “Molecule of the Year” for 1992”. While going through the literatures regarding the role of Nitric oxide in the tumor cells it becomes very clear that it has dual role depending upon the concentration of the substance involving in the blood stream and cell activities.[ Lala, Orucevic. 1998 ] has noted that “The role of Nitric oxide [NO] in tumoric-genesis is multifactorial./ NO could participate in the complicated process of carcino-genesis by mediating DNA damage in early phases of tumorigenesis, support tumor progression through the induction of angiogenesis and the suppression of the immune response . More over Maeda, Akaide [1998] has noted that “oxygen radicals and nitrogen oxide derivatives such as peroxynitrite and NO can effectively damage DNA despite the presence of multiple antioxidant defense and repair systems. Such damage is thought to make a significant contribution to the age-related development of cancer. Ambsetal, [1997 ] says that “”increased NO production may select mutant p53 cells and contribute to human carcinogenesis and tumor progression” The Role of Nitric Oxide 12 [ Lala, Orucevic, 1998] has noted that “the administration of NOS inhibitors in mice could decreas IL-2/No –induced capillary leakage and improve the IL-2-induced antitumor effector cell activation, stimulating by this way tumor regression”. He also argues by supporting the statement that NOS could be applied or administered in therapies for treating cancers and tumors cells, while NO will act as a toxic agent in aggravating the growth of the cancerous cells. The nitric oxide –releasing ability of the aspirin derivative NCX-4016 is enhanced by thiols, so I thought this type of treatment might work better in a tumor cancer cell that is rich in thiols, such as a resistant ovarian tumor cancer” [ Kuppusamy, Periannan.2006]. But still the experiments are in progression regarding the application of nitric oxide in the treatment therapies as controversies over the matter that nitric oxide is a toxic gas continues. On the whole one thing becomes clear that NOS can help in reducing the effect of the cancer and tumor cells, be it any type of cancer. Reference: Wright, Pearce. “Nitric Oxide: from Menace to marvel of the decade .online available form http://www.absw.org.uk/ May . 1996]. “Nitric Oxide Donors –agents in Cancer therapy” .online available from http://www.cellegy.com/science/Nitricoxide.html. 2006 Kuppusamy, Periannan . Comprehensive Cancer Center. Arthur G.James center Hospital and Richard J.Solove research Institute. Online available from http://reserachnews.osw.edu/archive/cisnitro.htm “The Role of Nitric oxide in tumor microcirculation.blood flow, vascular permeability, and leukocyte-endothelial interactions” The American Journal of Pathology Vol.150 713-725 [1997] online available from http://ajp.ampathol.org/cgi/contsnt/abstract/150/2/713 Weiming.X.U, Li Zhi LIU, Marilena Loizidou, Mohamed Ahmed and Ian G.Charles “The Role of Nitric Oxide in Cancer”[ review], 2002 online available from http://www.nature.com/cr/journal/v12/n5/abs/7290133a.html Murta B.M.T. , J.S. Machadom Zaparoli, V.C.Lara , E.F.C. Murta “The Relationship of host immune cells cytokines and nitric oxide production to tumor cells in ovarian carcinoma –Sao Paulo Med J .2 [1999] 87-92 online available from R.Alexandrova , M.Mileva, E.Zvetkova “Nitric Oxide and Cancer” a Minireview. http://www.iepp.bas.bg/EPP-vol%204%20[7]%2013-18.pdf Knowles. R.G., S. Moncada “Nitric oxide synthatase in mammals-Biochem.J. 298 [1994] 249-258 . online available from R.Alexandrova , M.Mileva, E.Zvetkova “Nitric Oxide and Cancer” a Minireview. http://www.iepp.bas.bg/EPP-vol%204%20[7]%2013-18.pdf De Belder.A.J, M.W. Radomski, nitric oxide in a clinical area J.Hypertension 12, 617-624 [1994]. online available from R.Alexandrova , M.Mileva, E.Zvetkova “Nitric Oxide and Cancer” a Minireview. http://www.iepp.bas.bg/EPP-vol%204%20[7]%2013-18.pdf “Ovarian Cancer”.online available from http://en.wikiepedia.edu/topic/ovariancancer .2006 Gale, Thomas . “Endocrine System Tumors”, Cancer Encyclopedia .online available from http://www.answers.com/topic/endocrine-system-tumors/ Gale, Thomas. “Ovarian Cancer”. Cancer Encyclopedia. Online available from http://www.answers.com/topic/ovarian-cancer 2006 “Ovarian Cancer Overview”.online available frm http://www.emedicinehealth.com/ovarian_cancer/article_em.htm. 2006 Maeda.H, T.Akaide. Nitric Oxide and oxygen Radicals in Infection, Inflammation and Cancer Biochemoistry [Moscow-7] 1007-1019. [1998] online available from R.Alexandrova , M.Mileva, E.Zvetkova “Nitric Oxide and Cancer” a Minireview. http://www.iepp.bas.bg/EPP-vol%204%20[7]%2013-18.pdf Lala P.K.,A. Orucevic. Role of Nitric Oxide in Tumor Progression :lessons form experimental tumors –Cancer Metastasis Rev. 17 -1998 91-106. online available from R.Alexandrova , M.Mileva, E.Zvetkova “Nitric Oxide and Cancer” a Minireview. http://www.iepp.bas.bg/EPP-vol%204%20[7]%2013-18.pdf Sherwood. W. Peter “Scientist Reveal role for Nitric Oxide During Brain Development .online available from http://www.cshl.edu/ November 14th .2001] P53 Mutation Database Analysis and Search. Online available from http://p53.genome.ad.jp/documents/about_p53.html NO can activate p53”. Online available from http://www.pnas.org/cgi/content/abstract/93/6/2442 Read More